The present invention relates to novel carboxylic acid derivatives, their preparation and use.
Endothelin is a peptide made up of 21 amino acids, which is synthesized and released by vascular endothelin. Endothelin exists in three isoforms, ET-1, ET-2 and ET-3. In the following, endothelin or ET designates one or all isoforms of endothelin. Endothelin is a potent vasoconstrictor and has a strong effect on the vascular tone. It is known that this vasoconstriction is caused by the binding of endothelin to its receptor (Nature, 332 (1988), 411-415; FEBS Letters, 231 (1988), 440-444, and Biochem. Biophys. Res. Commun., 154 (1988), 868-875).
Increased or abnormal release of endothelin causes a lasting vascular contraction in peripheral, renal and cerebral blood vessels which can lead to illnesses. As reported in the literature, endothelin is involved in a number of illnesses. These include: hypertension, acute myocardial infarct, pulmonary hypertension, Raynaud""s Syndrome, cerebral vasospasms, stroke, benign prostate hypertrophy, atherosclerosis and asthma (J. Vascular Med. Biology 2 (1990), 207, J. Am. Med. Association 264 (1990), 2868, Nature 344 (1990), 114, N. Engl. J. Med. 322 (1989), 205, N. Engl. J. Med. 328 (1993), 1732, Nephron 66 (1994), 373, Stroke 25 (1994), 904, Nature 365 (1993), 759, J. Mol. Cell. Cardiol. 27 (1995), A234; Cancer Research 56 (1996), 663).
At least two endothelin receptor subtypes, ETA and ETB receptors, are at present described in the literature (Nature 348 (1990), 730, Nature 348 (1990), 732). Accordingly, substances which inhibit the binding of endothelin to one or to both receptors should antagonize physiological effects of endothelin and therefore be useful pharmaceuticals.
It is an object of the present invention to make available endothelin receptor antagonists which bind to the ETA and/or the ETB receptors.
The invention relates to carboxylic acid derivatives of the formula I 
[lacuna] R1 is tetrazole or a group 
where R has the following meanings:
a) a radical OR6, where R6 is:
hydrogen, the cation of an alkali metal, the cation of an alkaline earth metal, a physiologically tolerable organic ammonium ion such as tertiary C1-C4-alkylammonium or the ammonium ion;
C3-C8-cycloalkyl, C1--C8-alkyl, CH2-phenyl which can be substituted by one or more of the following radicals: halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, hydroxyl, C1-C4-alkoxy, mercapto, C1-C4-alkylthio, amino, NH(C1-C4-alkyl), N(C1-C4-alkyl)2;
a C3-C8-alkenyl or a C3-C8-alkynyl group, it being possible for these groups in turn to carry one to five halogen atoms;
R6 can furthermore be a phenyl radical which can carry one to five halogen atoms and/or one to three of the following radicals: nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, hydroxyl, C1-C4-alkoxy, mercapto, C1-C4-alkylthio, amino, NH(C1-C4-alkyl), N(C1-C4-alkyl)2;
b) a 5-membered heteroaromatic linked via a nitrogen atom, such as pyrrolyl, pyrazolyl, imidazolyl or triazolyl, which can carry one to two halogen atoms, or one to two C1-C4-alkyl or one to two C1-C4-alkoxy groups;
c) a group 
where k [lacuna] assume the values 0, 1 and 2, p can assume the values 1, 2, 3 and 4 and R7 is
C1-C4-alkyl, C3-C8-cycloalkyl, C3-C8-alkenyl, C3-C8-alkynyl or phenyl, which can be substituted by one or more, eg. one to three, of the following radicals: halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, hydroxyl, C1-C4-alkoxy, C1-C4-alkylthio, mercapto, amino, NH(C1-C4-alkyl), N(C1-C4-alkyl)2;
d) a radical 
where R8 is:
C1-C4-alkyl, C3-C8-alkenyl, C3-C8-alkynyl, C3-C8-cycloalkyl, it being possible for these radicals to carry a C1-C4-alkoxy, C1-C4-alkylthio and/or a phenyl radical as mentioned under c);
C1-C4-haloalkyl or unsubstituted or substituted phenyl, in particular as mentioned under c).
The other substituents have the following meanings:
X is nitrogen or methine; with the proviso that if X=nitrogen then Z=nitrogen and if X=methine then at least one of the ring members Y or Z is nitrogen;
Y is nitrogen or CR9;
Z is nitrogen or CR10;
R2 is C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, it being possible for these radicals each to be mono- or polysubstituted by: halogen, hydroxyl, mercapto, carboxyl, cyano, amino, C1-C4-alkoxy;
hydrogen, halogen, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C6-alkenyloxy, C3-C6-alkynyloxy, C1-C4-alkylthio, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, hydroxyl, carboxyl, cyano, amino, mercapto;
or CR2 together with CR9 or CR10 forms a 5- or 6-membered alkylene or alkenylene ring which can be substituted by one or two C1-C4-alkyl groups, and where in each case one or more methylene groups can be replaced by oxygen, sulfur, xe2x80x94NH or xe2x80x94N(C1-C4-alkyl);
R3 and R4 (which can be identical or different) are:
phenyl or naphthyl, which can be substituted by one or more of the following radicals: halogen, nitro, cyano, hydroxyl, mercapto, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C1-C4-alkoxy, phenoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, amino, NH(C1-C4-alkyl), N(C1-C4-alkyl)2 or phenyl, which can be mono- or polysubstituted, eg. mono- to trisubstituted by halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or C1-C4-alkylthio; or
phenyl or naphthyl, which are connected to one another in the ortho position via a direct bond, a methylene, ethylene or ethenylene group, an oxygen or sulfur atom or an SO2xe2x80x94, NHxe2x80x94 or N-alkyl group;
C3-C8-cycloalkyl, it being possible for these radicals in each case to be mono- or polysubstituted by: halogen, hydroxyl, mercapto, carboxyl, nitro, cyano, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkoxy;
R5 is hydrogen, C1-C8-alkyl, C3-C8-alkenyl or C3-C8-alkynyl, it being possible for these radicals in each case to be mono- or polysubstituted by: halogen, hydroxyl, mercapto, carboxyl, nitro, amino, cyano, C1-C4-alkoxy, C3-C6-alkenyloxy, C3-C6-alkynyloxy, C1-C4-alkylthio, C1-C4-haloalkoxy, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, C3-C8-alkylcarbonylalkyl, NH(C1-C4-alkyl), N(C1-C4-alkyl)2,
C3-C8-cycloalkyl, heteroaryloxy or heteroaryl, which is five-or six-membered, comprising one to three nitrogen atoms and/or a sulfur or oxygen atom, phenoxy or phenyl, it being possible for the aryl radicals mentioned in turn to be mono- or polysubstituted, eg. mono- to trisubstituted by halogen, hydroxyl, mercapto, carboxyl, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, amino, NH(C1-C4-alkyl), N(C1-C4-alkyl)2 or C1-C4-alkylthio;
phenyl or naphthyl, which in each case can be substituted by one or more of the following radicals: halogen, nitro, cyano, hydroxyl, amino, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenoxy, C1-C4-alkylthio, C1-C4-alkylamino, C1-C4-dialkylamino, dioxomethylene or dioxoethylene;
a five- or six-membered heteroaromatic, comprising one to three nitrogen atoms and/or a sulfur or oxygen atom, which can carry one to four halogen atoms and/or one to two of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, phenyl, phenoxy or phenylcarbonyl, it being possible for the phenyl radicals in turn to carry one to five halogen atoms and/or one to three of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and/or C1-C4-alkylthio;
C3-C8-cycloalkyl, it being possible for these radicals in each case to be mono- or polysubstituted by: halogen, hydroxyl, mercapto, carboxyl, nitro, cyano, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkoxy;
R9 and R10 (which can be identical or different) are:
hydrogen, halogen, C1-C4-alkoxy, C1-C4-haloalkoxy, C3-C6-alkenyloxy, C3-C6-alkynyloxy, C1-C4-alkylthio, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, NH2, NH(C1-C4-alkyl), N(C1-C4-alkyl)2;
C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, it being possible for these radicals to be substituted by halogen, hydroxyl, mercapto, carboxyl, cyano;
or CR9 or CR10 is linked with CR2 as indicated under R2 to give a 5- or 6-membered ring;
W is sulfur, oxygen or a single bond;
Q is oxygen or nitrogen; with the proviso that if Q=nitrogen then W is a single bond.
In this context and subsequently the following definitions apply:
an alkali metal is, for example, lithium, sodium, potassium;
an alkaline earth metal is, for example, calcium, magnesium, barium;
organic ammonium ions are protonated amines such as, for example, ethanolamine, diethanolamine, ethylendiamine diethylamine or piperazine;
C3-C8-cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl;
C1-C4-haloalkyl can be linear or branched such as, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, trichloromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl or pentafluoroethyl;
C1-C4-haloalkoxy can be linear or branched such as, for example, difluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy, 1-fluoroethoxy, 2,2-difluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-1,1,2-trifluoroethoxy, 2-fluoroethoxy or pentafluoroethoxy;
C1-C4-alkyl can be linear or branched such as, for example, ethyl, ethyl, 1-propyl, 2-propyl, 2-methyl-2-propyl, 2-methyl-1-propyl, 1-butyl or 2-butyl;
C2-C4-alkenyl can be linear or branched such as, for example, ethenyl, 1-propen-3-yl, 1-propen-2-yl, 1-propen-1-yl, 2-methyl-1-propenyl, 1-butenyl or 2-butenyl;
C2-C4-alkynyl can be linear or branched such as, for example, ethynyl, 1-propyn-1-yl, 1-propyn-3-yl, 1-butyn-4-yl or 2-butyn-4-yl;
C1-C4-alkoxy can be linear or branched such as, for example, methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy or 1,1-dimethylethoxy;
C3-C6-alkenyloxy can be linear or branched such as, for example, allyloxy, 2-buten-1-yloxy or 3-buten-2-yloxy;
C3-C6-alkynyloxy can be linear or branched such as, for example, 2-propyn-1-yloxy, 2-butyn-1-yloxy or 3-butyn-2-yloxy;
C1-C4-alkylthio can be linear or branched such as, for example, methylthio, ethylthio, propylthio, 1-methylethylthio, butylthio, 1-methylpropylthio, 2-methylpropylthio or 1,1-dimethylethylthio;
C1-C4-alkylcarbonyl can be linear or branched such as, for example, acetyl, ethylcarbonyl or 2-propylcarbonyl;
C1-C4-alkoxycarbonyl can be linear or branched such as, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl or n-butoxycarbonyl;
C3-C8-alkylcarbonylalkyl can be linear or branched, for example 2-oxoprop-1-yl, 3-oxobut-1-yl or 3-oxobut-2-yl;
C1-C8-alkyl can be linear or branched such as, for example, C1-C4-alkyl, pentyl, hexyl, heptyl or octyl; C3-C8-alkenyl can be linear or branched such as, for example, 1-propen-3-yl, 1-propen-2-yl, 1-propen-1-yl, 2-methyl-1-propenyl, 1-buten-4-yl, 2-buten-3-yl, 1-penten-5-yl, 1-hexen-6-yl, 3-hexen-6-yl, 2-hepten-7-yl or 1-octen-8-yl;
C3-C8-alkynyl can be linear or branched such as, for example, 1-propyn-1-yl, 1-propyn-3-yl, 1-butyn-4-yl, 2-butyn-4-yl, 2-pentyn-5-yl, 3-hexyn-6-yl, 3-heptyn-7-yl, 2-octyn-8-yl;
halogen is, for example, fluorine, chlorine, bromine, iodine.
The invention further relates to those compounds from which the compounds of the formula I can be released (prodrugs).
Those prodrugs are preferred in which the release proceeds under conditions of the type which prevail in certain body compartments, eg. in the stomach, intestine, blood circulation, liver.
The compounds I and also the intermediates for their preparation, such as, for example, II, III, IV and V, can have one or more asymmetrically substituted carbon atoms. Compounds of this type can be present as pure enantiomers or pure diastereomers or as a mixture thereof. The use of an enantiomeric pure compound as the active compound is preferred.
The invention further relates to the use of the abovementioned carboxylic acid derivatives for the production of drugs, in particular for the production of inhibitors for ETA and/or ETB receptors. The compounds according to the invention are suitable as antagonists, as were defined at the outset.
The preparation of the compounds of the general formula IV, where W is sulfur or oxygen and Q is oxygen (IVa) can be carried out, also in enantiomerically pure form, as described in WO 96/11914. 
Compounds of the general formula III are either known or can be synthesized, for example, by reduction of the corresponding carboxylic acids or their esters, or by other generally known methods.
The compounds of the general formula IV, where W is a single bond and Q is oxygen (VIb), can be prepared both in racemic and in enantiomerically pure form as described in DE 19614533.3.
On the other hand, the compounds of the general formula IV, where W is a single bond and Q is nitrogen (IVc) can be prepared both in racemic form and in enantiomerically pure form as described in DE 19536891.6. 
The compounds according to the invention, where the substituents have the meanings indicated under the general formula I, can be prepared, for example, by reacting the carboxylic acid derivatives of the general formula IV, in which the substituents have the meanings indicated, with compounds of the general formula VII. 
In formula VII, R11 is halogen or R12xe2x80x94SO2xe2x80x94, it being possible for R12 to be C1-C4-alkyl, C1-C4-haloalkyl or phenyl, and for X, Y and Z the conditions mentioned at the outset apply. The reaction preferably takes place in an inert solvent or diluent with addition of a suitable base, ie. of a base which brings about deprotonation of the intermediate IV, in a temperature range from room temperature up to the boiling point of the solvent.
Compounds of the type I where R1=COOH can furthermore be obtained directly if the intermediate IV, where R1 is COOH, is deprotonated using two equivalents of a suitable base and reacted with compounds of the general formula V. Here also, the reaction takes place in an inert solvent and in a temperature range from room temperature up to the boiling point of the solvent.
Examples of solvents or diluents of this type are aliphatic, alicyclic and aromatic hydrocarbons, which in each case can be free or chlorinated, such as, for example, hexane, cyclohexane, petroleum ether, naphtha, benzene, toluene, xylene, methylene chloride, chloroform, carbon tetrachloride, ethyl chloride and trichloroethylene, ethers, such as, for example, diisopropyl ether, dibutyl ether, methyl tert-butyl ether, propylene oxide, dioxane and tetrahydrofuran, nitrites, such as, for example, acetonitrile and propionitrile, acid amides, such as, for example, dimethylformamide, dimethylacetamide and N-methylpyrrolidone, sulfoxides and sulfones, such as, for example, dimethyl sulfoxide and sulfolane.
Compounds of the formula VII are known, in some cases commercially available or can be prepared in a generally known manner (eg. in a similar manner to J. Org. Chem. 52 (1987), 4280).
The base used can be an alkali metal or alkaline earth metal hydride, such as sodium hydride, potassium hydride or calcium hydride, a carbonate such as an alkali metal carbonate, eg. sodium or potassium carbonate, an alkali metal or alkaline earth metal hydroxide such as sodium or potassium hydroxide, an organometallic compound such as butyllithium or an alkali metal amide such as lithium diisopropylamide or lithium amide.
Compounds of the formula I can also be prepared by starting from the corresponding carboxylic acids, ie. compounds of the formula I where R1 is COOH, and first converting these in a customary manner into an activated form such as an acid halide, an anhydride or imidazolide and then reacting this with an appropriate hydroxyl compound HOR7. This reaction can be carried out in the customary solvents and often requires the addition of a base, those mentioned above being suitable. These two steps can also be simplified, for example, by allowing the carboxylic acid to act on the hydroxyl compound in the presence of a dehydrating agent such as a carbodiimide.
Moreover, compounds of the formula I can also be prepared by starting from the salts of the corresponding carboxylic acids, ie. from compounds of the formula I where R1 is COR and R is OM, it being possible for M to be an alkali metal cation or the equivalent of an alkaline earth metal cation. These salts can be reacted with many compounds of the formula R-A, A being a customary nucleofugic leaving group, for example halogen such as chlorine, bromine, iodine or, if desired, aryl- or alkylsulfonyl substituted by halogen, alkyl or haloalkyl, such as, for example, toluenesulfonyl and methylsulfonyl or another equivalent leaving group. Compounds of the formula R-A having a reactive substituent A are known or easy to obtain using the general expert knowledge. This reaction can be carried out in the customary solvents and is advantageously performed with addition of a base, those mentioned above being suitable.
Compounds of the formula I where R1 is tetrazole can be prepared as described in WO 96/11914.
With respect to the biological action, carboxylic acid derivatives of the general formula I, both as pure enantiomers and pure diastereomers or as a mixture thereof, are preferred where the substituents have the following meanings:
X is nitrogen or methine; with the proviso that if X=nitrogen then Z=nitrogen and if X=methine then at least one of the ring members Y or Z=nitrogen;
Y is nitrogen or CR9;
Z is nitrogen or CR10;
R2 is C1-C4-alkyl, C2-C4-alkenyl, it being possible for these radicals each to be mono- to trisubstituted by: halogen, hydroxyl, mercapto;
hydrogen, halogen, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-alkoxycarbonyl, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, hydroxyl;
or CR2, together with CR9 or CR10, forms a 5- or 6-membered alkylene or alkenylene ring which can be substituted by one or two C1-C4-alkyl groups, and where in each case one or more methylene groups can be replaced by oxygen, sulfur, xe2x80x94NH or xe2x80x94N(C1-C4-alkyl);
R3 and R4 (which can be identical or different) are:
phenyl or naphthyl, it being possible for these radicals to be mono- to trisubstituted by: halogen, cyano, hydroxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, amino, NH(C1-C4-alkyl), N(C1-C4-alkyl)2 or phenyl, which can be mono- to trisubstituted by halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or C1-C4-alkylthio; or
phenyl or naphthyl, which are bonded to one another in the ortho position via a direct bond, a methylene, ethylene or ethenylene group, an oxygen or sulfur atom or an SO2xe2x80x94, NHxe2x80x94 or N-alkyl group;
C3-C8-cycloalkyl, it being possible for these radicals in each case to be mono- to trisubstituted by: halogen, hydroxyl, mercapto, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkoxy;
R5 is hydrogen, C1-C8-alkyl, C3-C8-alkenyl or C3-C8-alkynyl, it being possible for these radicals in each case to be mono- to trisubstituted by: halogen, hydroxyl, mercapto, carboxyl, amino, cyano, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkoxy, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, C3-C8-cycloalkyl, heteroaryloxy or heteroaryl, five- or six-membered, comprising one to three nitrogen atoms and/or a sulfur or oxygen atom, phenoxy or phenyl, it being possible for the aryl radicals mentioned in turn to be mono- to trisubstituted by halogen, hydroxyl, mercapto, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, NH(C1-C4-alkyl) or N(C1-C4-alkyl)2;
phenyl or naphthyl, which in each case can be mono- to trisubstituted by: halogen, cyano, hydroxyl, amino, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenoxy, C1-C4-alkylthio, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, dioxomethylene or dioxoethylene;
a five- or six-membered heteroaromatic, comprising one to three nitrogen atoms and/or a sulfur or oxygen atom which can carry one to four halogen atoms and/or one to two of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, phenyl, phenoxy or phenylcarbonyl, it being possible for the phenyl radicals in turn to carry one to five halogen atoms and/or one to three of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, Cl-C4-alkoxy, C1-C4-haloalkoxy and/or C1-C4-alkylthio;
C3-C8-cycloalkyl, it being possible for these radicals in each case to be mono- to trisubstituted by: halogen, hydroxyl, mercapto, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-haloalkoxy;
R9 and R10 (which can be identical or different) are:
hydrogen, halogen, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, NH2, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, hydroxyl;
C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, it being possible for these radicals to be substituted by halogen, hydroxyl, mercapto, cyano;
or CR9 or CR10 is linked to CR2 as indicated under R2 to give a 5- or 6-membered ring;
W is sulfur, oxygen or a single bond;
Q is oxygen or nitrogen, with the proviso that if Q=nitrogen then W is a single bond.
Particularly preferred compounds of the formula I, both as pure enantiomers and pure diastereomers or as a mixture thereof, are those in which the substituents have the following meanings:
X is nitrogen or methine; with the proviso that if X=nitrogen then Z=nitrogen and Y=CR9 and if X=methine then Y=nitrogen and Z=CR10 or Y=CR9 and Z=nitrogen;
Y is nitrogen or CR9;
Z is nitrogen or CR10;
R2 is C1-C4-alkyl, trifluoromethyl, hydrogen, fluorine, C1-C4-alkoxy, trifluoromethoxy, C1-C4-alkylthio;
or CR2, together with CR9 or CR10, forms a 5- or 6-membered alkylene or alkenylene ring, which can be substituted by one or two C1-C4-alkyl groups, and where in each case one or more methylene groups can be replaced by oxygen or sulfur;
R3 and R4 (which can be identical or different) are:
phenyl or naphthyl, which can be substituted by one or more of the following radicals: halogen, cyano, C1-C4-alkyl, trifluoromethyl, C1-C4-alkoxy, trifluoromethoxy, C1-C4-alkylthio or phenyl, which can be mono- to trisubstituted by halogen, C1-C4-alkyl, trifluoromethyl, C1-C4-alkoxy or C1-C4-alkylthio; or
phenyl or naphthyl, which are connected in the ortho position via a direct bond, a methylene, ethylene or ethenylene group;
C5-C6-cycloalkyl, it being possible for these radicals in each case to be mono- to trisubstituted by: halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio;
R5 is hydrogen, C1-C8-alkyl, C3-C8-alkenyl or C3-C8-alkynyl, it being possible for these radicals in each case to be mono- to trisubstituted by: halogen, hydroxyl, mercapto, carboxyl, cyano, amino, C1-C4-alkoxy, C1-C4-alkylthio, C1-C4-alkoxycarbonyl, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, C3-C8-cycloalkyl, heteroaryloxy or heteroaryl, five- or six-membered, comprising one to three nitrogen atoms and/or a sulfur or oxygen atom, phenoxy or phenyl, it being possible for the aryl radicals mentioned in turn to be mono- to trisubstituted by halogen, cyano, hydroxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio or N(C1-C4-alkyl)2; 
phenyl or naphthyl, which in each case can be mono- to trisubstituted by: halogen, C1-C4-alkyl, trifluoromethyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenoxy, C1-C44-alkylthio, dioxomethylene or dioxoethylene;
a five- or six-membered heteroaromatic, comprising one to three nitrogen atoms and/or a sulfur or oxygen atom, which can carry one to four halogen atoms and/or one to two of the following radicals: C1-C4-alkyl, trifluoromethyl, C1-C4-alkoxy, C1-C4-alkylthio, phenyl, phenoxy, it being possible for the phenyl radicals in turn to carry one to five halogen atoms and/or one to three of the following radicals: C1-C4-alkyl, C1-C4-alkoxy or C1-C4-alkylthio;
C3-C8-cycloalkyl, it being possible for these radicals in each case to be mono- to trisubstituted by: halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio;
R9 and R10 (which can be identical or different) are:
trifluoromethyl, trifluoromethoxy, hydrogen, C1-C4-alkoxy, C1-C4-alkylthio, NH(C1-C4-alkyl), N(C1-C4-alkyl)2, C1-C4-alkyl, vinyl;
or CR9 or CR10 is linked to CR2 as indicated under R2 to give a 5- or 6-membered ring;
W is sulfur, oxygen or a single bond;
Q is oxygen or nitrogen; with the proviso that if Q=nitrogen then W is a single bond.